Project 1: SCD Abstract: Epidemiologic evidence suggests that subjective memory complaints in aging confer some degree of risk for subsequent cognitive decline and/or progression to dementia. There is also accumulating evidence that Alzheimer Disease (AD)-biomarkers, including amyloid-beta (A) pathology, are associated with subjective cognitive complaints in otherwise healthy older individuals a clinical state described as Subjective Cognitive Decline (SCD). In the AD research community, growing interest in SCD as potentially the earliest detectable symptoms of AD is further fueled by the goal of increasingly earlier identification of risk in intervention and secondary prevention trials. However, a boundary shift of preclinical AD closer toward normal cognitive aging poses many challenges. Subjective memory complaints and concerns are common, perhaps even normative, among older adults. To date, we lack informative data addressing how to best to distinguish among etiologies of subjective cognitive complaints, including normal cognitive aging. Individual differences in personality traits and mood symptoms are known to be important correlates of subjective cognitive complaints; how these psychological factors interact and whether they are independent of underlying AD pathophysiology is not yet understood. The goal of the proposed Project is to further knowledge about how SCD and A pathology may be associated. To achieve this, we will recruit and study a sample of 56 older volunteers who have presented in a medical setting with concerns about memory or other cognitive decline, but who also have normal objective test performance. We will test the hypothesis that SCD is associated with a higher proportion of A-positive individuals, as assessed by Pittsburgh compound B (PiB)- PET imaging, compared to age- and education-matched cognitively normal controls without presenting concerns. Further, we hypothesize that A-positive (compared to A-negative) SCD will be associated with 1) questionnaire-measured variables, including the personality trait `emotional instability (i.e.,`neuroticism'), episodic memory complaints and degree of dysfunction in daily life; and 2) other AD-biomarker variables reflective of brain changes, including structural and functional MRI, and subtle deficits on more challenging cognitive tests. To the degree possible, an exploratory aim is to compare rates of incident mild cognitive impairment (MCI) through Clinical Core follow-up, as a function of baseline A status. This Project will provide the foundation for further longitudinal study, with the longer-term goal of determining which biomarker and psychological features of SCD are predictive of clinical progression to MCI and AD. Findings from this Project will further inform models of the AD-pathophysiological sequence in relation to very early behavioral and symptomatic change.